Scientific title:

The Impact of using FilmArray Pneumonia Panel Molecular Diagnostics for Hospital-Acquired and Ventilator-Associated Pneumonia on Antimicrobial Stewardship and Patient Outcomes in UK Critical Care: A Multicentre Randomised Controlled Trial.

Chief Investigator:

Prof David Livermore and Dr ​​Vanya Gant

Funder:

This research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Reference Number RP-PG-0514-20018).

The views expressed are those of the Inhale Team and not necessarily those of the NHS, the NIHR or the Department of Health.

Sponsor:

UCL

Health condition studied:

Hospital Acquired and Ventilator Associated Pneumonia (HAP and VAP) in UK critical care

Intervention:

Treatment guided by the BioFire FilmArray molecular diagnostic machine (The “FilmArray test”), a PCR-based pathogen and bacterial resistance detection system for identifying candidate pathogens driving lower respiratory infections, together with a trial-based prescribing algorithm adapted to accommodate site-specific requirements where appropriate. Treatment will follow standard care with the aim of moving to intervention-guided prescribing as soon as results are available (machine test time is 1-2h)

Control:

Standard care, which consists of empirical antibiotics, based on local policy and adapted once microbiology culture and susceptibility testing results are available (typically after 48-72 h)

Study design:

This interventional trial is an open-label, parallel, randomised controlled trial exploring the potential of FilmArray molecular diagnostics versus standard care.

Target sample size:

Actual size: 558

Status:

Follow-up

Background:

INHALE is a programme grant. It tackles the issue of antimicrobial stewardship and antibiotic resistance. Severely ill hospital patients often develop pneumonia; to treat this effectively, with the right antibiotic, doctors must know the type of bacteria responsible. Secretions from the lungs and respiratory tract are sent to the laboratory to identify the bacteria and to see which antibiotics kill them.

Testing takes 2 days or more, and a so-called “broad-spectrum antibiotic”, capable of killing many different types of bacteria, is given until the results become available. This isn’t ideal. Some patients with pneumonia symptoms don’t have bacterial infection. Some have highly resistant bacteria, not killed even by broad-spectrum antibiotics; this doubles the risk of death in severe pneumonia. Broad-spectrum antibiotics promote undesirable side effects too, for example C diff diarrhoea, and can increase resistance, making future infections harder to treat. Many pneumonia patients have very susceptible bacteria and are ‘over-treated’ until the lab result becomes available.

New ‘molecular diagnostic’ tests, which work by identifying bacteria directly from their genetic material present in a clinical sample, claim to identify bacteria and their resistances within 1-4 hours. This would allow treatments to be optimised earlier, benefitting individual patients and allowing the most potent antibiotics to be reserved for those who really need them. However, we don’t know how well these tests compare with current methods, whether they find all the important types of resistant bacteria, whether they represent value for money, or whether doctors will accept the results and use the tests.

INHALE addresses these important questions.

The first part of the programme grant collected samples from patients with suspected pneumonia in the intensive care units of 18 English hospitals, carefully chosen to represent a cross section of healthcare. Samples were tested on three new molecular diagnostic systems; to see how accurate they were and how easy they were to use. The systems were not used to guide treatment, only to select the best one for the next stage of the study.

The best performing system was taken forward into a randomised controlled trial where it was compared to routine microbiology testing (standard care). INHALE WP3 is a multicentre randomised controlled trial designed to examine the clinical, safety and cost effectiveness of a FilmArray molecular diagnostic pneumonia panel (used to determine the presence of common HAP and VAP causing pathogens), its prescribing algorithm, and their effect on patient outcomes and antimicrobial stewardship in UK critical care.

It includes a cost effectiveness analysis (WP5) to see whether the outcomes justify the costs and a behavioural analysis (WP4) to see whether clinicians are willing to base treatments on molecular results. This will identify the barriers to introducing molecular diagnostics and how these can be overcome.

The trial aims to show at least equivalence between the two groups in terms of clinical cure of pneumonia and superiority in antimicrobial stewardship.

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